title: Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90.
abstract: The 90-kDa heat shock protein (HSP90) is a molecular chaperone that assists in the folding and assembly of proteins in the cytosol. We previously demonstrated that the antineoplastic reagent, cisplatin, inhibits the aggregation prevention activity of mammalian HSP90. We now show that cisplatin binds both the amino terminal and carboxyl terminal domains of the human HSP90 and differently affects these two domains. Cisplatin blocks the aggregation prevention activity of HSP90C, but not HSP90N. In contrast, cisplatin induces a conformational change in HSP90N, but not HSP90C. These results indicate that cisplatin modulates the HSP90 activities through two different mechanisms using the two distinct binding sites of the HSP90 molecule.
authors.affiliation: Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita 010-8502, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Ishida
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takaoka
authors.forename: Soh
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
authors.forename: Atushi
authors.initials: A
authors.lastname: Komatsuda
authors.forename: Hideki
authors.initials: H
authors.lastname: Wakui
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Sawada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubota
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
mesh_terms: D020816:Amino Acid Motifs; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D017434:Protein Structure, Tertiary / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D002945:Cisplatin